Plant ion channels: gene families, physiology, and functional genomics analyses

Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization- and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide-gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport.

Low bone mass in idiopathic renal stone formers: magnitude and significance

To assess bone mineral density (BMD) in idiopathic calcium nephrolithiasis, dual-energy x-ray absorptiometry was performed at lumbar spine, upper femur (femoral neck, Ward's triangle, and total area), distal tibial diaphysis, and distal tibial epiphysis in 110 male idiopathic calcium stone formers (ICSF); 49 with and 61 without hypercalciuria on free-choice diet). Results were compared with those obtained in 234 healthy male controls, using (1) noncorrected BMD, (2) BMD corrected for age, height, and BMI, and (3) a skeletal score based on a tercile distribution of BMD values at following four sites: lumbar spine, Ward's triangle, tibial diaphysis, and tibial epiphysis. After correction, BMD--and therefore also skeletal score--tended to be lower in the stone formers than in controls at five of the six measurement sites, that is, lumbar spine, upper femur, Ward's triangle, tibial diaphysis, and tibial epiphysis, limit of significance being reached for the last two sites without difference between hypercalciuric (HCSF) and normocalciuric stone formers (NCSF). Estimated current daily calcium intake was significantly lower in patients (616 +/- 499 mg/24 h, mean +/- SEM) than in controls (773 +/- 532, p = 0.02). Of 17 patients who in the past had received a low-calcium diet for at least 1 year, 10 had a low skeletal score (4-6) whereas only 1 had a high score (10-12; p = 0.037). Of the 12 stone formers in the study with skeletal score 4 (i.e., the lowest), 8 had experienced in the past one or more fractures of any kind versus only 19 of the remaining 77 patients with skeletal score 5-12 (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The Care and Shelter of Children and Adolescents in Brazil: Expressions of Social Issues

The future of Brazilian children who have the protection offered by familial bonds is threatened by social inequities that force them to seek shelter and grow up in shelters. According to the Institute of Applied Economic Research, an estimated 20,000 children and adolescents are served by institutions. The majority of these children are afro-descendent males between the ages of seven and fifteen years old. Of those researched, 87.6% have families (58.2% receive visits from their families, 22.7% are rarely visited by their families and 5.8 are legally prohibited from contacting or being by their families). The percentage of children and adolescents “without families” or with “missing families” is 11.3%. There is no information available for 2% of the children and adolescents residing in shelters. The principle factors that necessitate the placement of Brazilian children in institutions that provide care and shelter include poverty (including children forced to work, sell drugs or beg, for example); domestic violence; chemical dependence of parents or guardians; homelessness; death or parents or guardian; imprisonment of their parents; and sexual abuse committed by their parents or guardians. The issue of abandoned children and adolescents and their care and shelter in the Brazilian context expresses a perverse violation of Child and Adolescent Rights.

Spin ladders and quantum simulators for Tomonaga–Luttinger liquids

Magnetic insulators have proven to be usable as quantum simulators for itinerant interacting quantum systems. In particular the compound (C5H12N)2CuBr4 (for short: (Hpip)2CuBr4) was shown to be a remarkable realization of a Tomonaga–Luttinger liquid (TLL) and allowed us to quantitatively test the TLL theory. Substitution weakly disorders this class of compounds and thus allows us to use them to tackle questions pertaining to the effect of disorder in TLL as well, such as that of the formation of the Bose glass. In this paper we present, as a first step in this direction, a study of the properties of the related (Hpip)2CuCl4 compound. We determine the exchange couplings and compute the temperature and magnetic field dependence of the specific heat, using a finite temperature density matrix renormalization group procedure. Comparison with the measured specific heat at zero magnetic field confirms the exchange parameters and Hamiltonian for the (Hpip)2CuCl4 compound, giving the basis needed to begin studying the disorder effects.

Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling

BACKGROUND Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification. OBJECTIVE To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs). DESIGN Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness. SETTING General population and genitourinary medicine clinic attenders. PARTICIPANTS Heterosexual women and men. INTERVENTIONS Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT). MAIN OUTCOME MEASURES Population prevalence; index case reinfection; and partners treated per index case. RESULTS Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, > 10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage. CONCLUSIONS There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Double Standards? Veils and Crucifixes in the European Legal Order

Comparing the treatment of Islamic veils and Christian crucifixes by the European Court of Human Rights, this paper re-examines the charge of “double standards” on the part of this guardian of the European legal order, which is seen as disadvantaging Islam and favoring Christianity. While this is proved partially correct, the paper calls for a more differentiated treatment of the issue. For one, there is a modicum of consistency in the European Court’s decisions, because they are all meant to further “pluralism”. Only, Islam and Christianity fare differently in this respect, as “threat” to and “affirmation” of pluralism, respectively. This distinction hinges on Islam’s compatibility with the liberal-secular order, on which the jury is out. A possible way out of the “pluralism v. pluralism” dilemma, I argue, is signaled in the European Court’s recent decision in Lautsi v. Italy (2011), which pairs a preference for “culturalized” Christianity with robust minority pluralism.

The need for transparency and good practices in the qPCR literature

Two surveys of over 1,700 publications whose authors use quantitative real-time PCR (qPCR) reveal a lack of transparent and comprehensive reporting of essential technical information. Reporting standards are significantly improved in publications that cite the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, although such publications are still vastly outnumbered by those that do not.

Creating a public tool to assess and promote transparency in global land deals: the experience of the Land Matrix

The Beta version of the Land Matrix (Land Matrix 2012) was launched in April 2012 as a tool to promote public participation in building a constantly evolving database on large-scale land deals, and making the data visible and understandable. The aim of the Land Matrix partnership is to promote transparency and open data in decisionmaking over land and investment, as a step towards greater accountability. Since its launch, the Land Matrix has attracted a high degree of attention, and stirred some controversy. It provides valuable lessons on the challenges and benefits of promoting open data on practices that are often shrouded in secrecy. This paper critically examines the ongoing efforts by the Land Matrix partnership to build a public tool to promote greater transparency in decision-making over land and investment at a global level. It intends to provoke discussion of the extent to which such a tool can ultimately promote greater transparency and be a step towards greater accountability and improved decision-making. It will present the Land Matrix and its value addition, before detailing the challenges it encountered related to the measurement of the largescale land acquisition phenomenon. It will then specify how it intends to address these issues in order to establish a dynamic and participatory tool for open development.

Dissecting the Interaction between p53 and TRIM24

Dissecting the Interaction of p53 and TRIM24 Aundrietta DeVan Duncan Supervisory Professor, Michelle Barton, Ph.D. p53, the “guardian of the genome”, plays an important role in multiple biological processes including cell cycle, angiogenesis, DNA repair and apoptosis. Because it is mutated in over 50% of cancers, p53 has been widely studied in established cancer cell lines. However, little is known about the function of p53 in a normal cell. We focused on characterizing p53 in normal cells and during differentiation. Our lab recently identified a novel binding partner of p53, Tripartite Motif 24 protein (TRIM24). TRIM24 is a member of the TRIM family of proteins, defined by their conserved RING, B-box, and coiled coil domains. Specifically, TRIM24 is a member of the TIF1 subfamily, which is characterized by PHD and Bromo domains in the C-terminus. Between the Coiled-coil and PHD domain is a linker region, 437 amino acids in length. This linker region houses important functions of TRIM24 including it’s site of interaction with nuclear receptors. TRIM24 is an E3-ubiquitin ligase, recently discovered to negatively regulate p53 by targeting it for degradation. Though it is known that Trim24 and p53 interact, it is not known if the interaction is direct and what effect this interaction has on the function of TRIM24 and p53. My study aims to elucidate the specific interaction domains of p53 and TRIM24. To determine the specific domains of p53 required for interaction with TRIM24, we performed co-immuoprecipitation (Co-IP) with recombinant full-length Flag-tagged TRIM24 protein and various deletion constructs of in vitro translated GST-p53, as well as the reverse. I found that TRIM24 binds both the carboxy terminus and DNA binding domain of p53. Furthermore, my results show that binding is altered when post-translational modifications of p53 are present, suggesting that the interaction between p53 and TRIM24 may be affected by these post-translational modifications. To determine the specific domains of TRIM24 required for p53 interaction, we performed GST pull-downs with in vitro translated, Flag-TRIM24 protein constructs and recombinant GST-p53 protein purified from E. coli. We found that the Linker region is sufficient for interaction of p53 and TRIM24. Taken together, these data indicate that the interaction between p53 and TRIM24 does occur in vitro and that interaction may be influenced by post-translational modifications of the proteins.

The influence of staff and organizational characteristics on social environment in substance abuse treatment facilities

The staff of 20 substance abuse treatment facilities were administered the Ward Atmosphere Scale, an instrument which measures treatment environment. Ten facilities were freestanding and ten were hospital based, and were drawn from a large, not-for-profit national chain using a random selection process. Controlling for several staff and facility attributes, it was found that no substantial effects on treatment environment existed due to facility type, freestanding or hospital-based. Implications of the study exist in selection of facility type for purchasers of substance abuse treatment and for the hiring and training of clinical staff for treatment facilities. Study findings also suggest that inadequate or insufficient measures exist to examine the construct 'treatment environment'. ^

AtPTR1, a plasma membrane peptide transporter expressed during seed germination and in vascular tissue of Arabidopsis

For the efficient translocation of organic nitrogen, small peptides of two to three amino acids are posited as an important alternative to amino acids. A new transporter mediating the uptake of di- and tripeptides was isolated from Arabidopsis thaliana by heterologous complementation of a peptide transport-deficient Saccharomyces cerevisiae mutant. AtPTR1 mediated growth of S. cerevisiae cells on different di- and tripeptides and caused sensitivity to the phytotoxin phaseolotoxin. The spectrum of substrates recognized by AtPTR1 was determined in Xenopus laevis oocytes injected with AtPTR1 cRNA under voltage clamp conditions. AtPTR1 not only recognized a broad spectrum of di- and tripeptides, but also substrates lacking a peptide bond. However, amino acids, omega-amino fatty acids or peptides with more than three amino acid residues did not interact with AtPTR1. At pH 5.5 AtPTR1 had an apparent lower affinity (K-0.5 = 416 mum) for Ala-Asp compared with Ala-Ala (K-0.5 = 54 mum) and Ala-Lys (K-0.5 = 112 mum). Transient expression of AtPTR1/GFP fusion proteins in tobacco protoplasts showed that AtPTR1 is localized at the plasma membrane. In addition, transgenic plants expressing the beta-glucuronidase (uidA) gene under control of the AtPTR1 promoter demonstrated expression in the vascular tissue throughout the plant, indicative of a role in long-distance transport of di- and tripeptides.

Optimizing Triage and Hospitalization in Adult General Medical Emergency Patients. The Triage Project

Background: Patients presenting to the emergency department (ED) currently face inacceptable delays in initial treatment, and long, costly hospital stays due to suboptimal initial triage and site-of-care decisions. Accurate ED triage should focus not only on initial treatment priority, but also on prediction of medical risk and nursing needs to improve site-of-care decisions and to simplify early discharge management. Different triage scores have been proposed, such as the Manchester triage system (MTS). Yet, these scores focus only on treatment priority, have suboptimal performance and lack validation in the Swiss health care system. Because the MTS will be introduced into clinical routine at the Kantonsspital Aarau, we propose a large prospective cohort study to optimize initial patient triage. Specifically, the aim of this trial is to derive a three-part triage algorithm to better predict (a) treatment priority; (b) medical risk and thus need for in-hospital treatment; (c) post-acute care needs of patients at the most proximal time point of ED admission. Methods/design: Prospective, observational, multicenter, multi-national cohort study. We will include all consecutive medical patients seeking ED care into this observational registry. There will be no exclusions except for non-adult and non-medical patients. Vital signs will be recorded and left over blood samples will be stored for later batch analysis of blood markers. Upon ED admission, the post-acute care discharge score (PACD) will be recorded. Attending ED physicians will adjudicate triage priority based on all available results at the time of ED discharge to the medical ward. Patients will be reassessed daily during the hospital course for medical stability and readiness for discharge from the nurses and if involved social workers perspective. To assess outcomes, data from electronic medical records will be used and all patients will be contacted 30 days after hospital admission to assess vital and functional status, re-hospitalization, satisfaction with care and quality of life measures. We aim to include between 5000 and 7000 patients over one year of recruitment to derive the three-part triage algorithm. The respective main endpoints were defined as (a) initial triage priority (high vs. low priority) adjudicated by the attending ED physician at ED discharge, (b) adverse 30 day outcome (death or intensive care unit admission) within 30 days following ED admission to assess patients risk and thus need for in-hospital treatment and (c) post acute care needs after hospital discharge, defined as transfer of patients to a post-acute care institution, for early recognition and planning of post-acute care needs. Other outcomes are time to first physician contact, time to initiation of adequate medical therapy, time to social worker involvement, length of hospital stay, reasons fordischarge delays, patient’s satisfaction with care, overall hospital costs and patients care needs after returning home. Discussion: Using a reliable initial triage system for estimating initial treatment priority, need for in-hospital treatment and post-acute care needs is an innovative and persuasive approach for a more targeted and efficient management of medical patients in the ED. The proposed interdisciplinary , multi-national project has unprecedented potential to improve initial triage decisions and optimize resource allocation to the sickest patients from admission to discharge. The algorithms derived in this study will be compared in a later randomized controlled trial against a usual care control group in terms of resource use, length of hospital stay, overall costs and patient’s outcomes in terms of mortality, re-hospitalization, quality of life and satisfaction with care.